The goals of the project are: 1) To produce continuously propagable murine cloned T cell lines and hybrids which release immune interferon (IFN-Gamma) and lymphotoxin (LT). 2) To distinguish between LT and IFN-Gamma physiologically, biochemically and antigenically. 3) To identify the cellular receptor(s) for IFN-Gamma and LT. 4) To determine whether one, or both, or a combination of LT and IFN-Gamma, prevent tumor development, particularly through inhibition of malignant transformation. Murine T cell clones will be grown in the presence of specific antigen, irradiated spleen cells and T cell growth factor (TCGF). Hybrids will be prepared by fusing clones with T lymphomas, thus maintaining antigen-specific T cell functions in the proliferating environment of the lymphoma. LT production will be evaluated by Coulter counter assay of surviving innocent bystander A9 or L929 cells. IFN-Gamma will be assayed by its acid sensitive inhibition of the cytopathic effect of vesicular stomatitis virus. IFN-Gamma and LT from cloned lines, which are less heterogeneous than lymphokines from bulk cultures, will be compared with regard to optimal conditions for induction, pH sensitivity, size and antigenic determinants. Monoclonal antibodies will be prepared against IFN-Gamma and LT to determine whether or not the growth inhibitory properties ascribed to IFN are due to contamination by LT. The cellular receptor(s) for murine INF-Gamma and LT will be identified with a monoclonal antibody against the IFN-Gamma receptor to be developed in this study. The effect of LT and IFN-Gamma on transformation by SV 40 virus will be assayed by monitoring expression of T antigen and growth in semisolid medium. If inhibition of either parameter occurs, the mechanism will be probed with monoclonal antibodies directed against the lymphokines and the cellular receptor(s). These studies will definitively distinguish between LT and IFN-Gamma and provide insight into their natural roles in delayed hypersensitivity, inhibition of viral replication and inhibition of tumor development.